Lidiia Zhytnik „Inter- and intrafamilial diversity based on genotype and phenotype correlations of Osteogenesis Imperfecta“

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View all other units

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Date:

15.10.2019 - 15:00

On 15 October at 15 Lidiia Zhytnik will defend her doctoral thesis „Inter- and intrafamilial diversity based on genotype and phenotype correlations of Osteogenesis Imperfecta“.

Supervisors:
Associate Professor in Orthopedics Katre Maasalu, Institute of Clinical Medicine
Professor in Pathophysiology Sulev Kõks, Institute of Biomedicine and Translational Medicine
Professor in Orthopedics Aare Märtson, Institute of Clinical Medicine

Opponent:
Assistant Professor Dimitra Micha (PhD), Department of Clinical Genetics, VU University Medical Center, Amsterdam, Holland

Summary
Osteogenesis Imperfecta (OI) is a rare genetic disorder, also known as a “brittle bone disease”. Patients’ phenotypes range from mild bone fragility to severe or even lethal cases. In up to 90% of cases the main target of the disorder is collagen type I.

Current thesis aimed to identify genotype-phenotype associations in OI families with inter- and intrafamilial phenotypical variability. We have investigated clinical characteristics and described spectrum of collagen-related mutations in OI patients. We have analyzed de novo cases among collagen-related OI patients and genotype-phenotype correlations in OI patients of Estonian, Ukrainian and Vietnamese origin. Further, we have performed genetic screening of non-collagen OI patients for a rare OI form - type V. Finally, inter- and intrafamilial diversity in collagen-related OI families was analyzed.

In Estonian population 90% of patients harbored collagen mutations. Out of them, majority had quantitative defect of the collagen I. Among Ukrainian OI patients, 64% had collagen I mutations, with almost equal amount of qualitative and quantitative collagen defects among them. Almost half of all identified OI mutations were undescribed previously. 57% of patients did not have OI family history and the disorder appeared as de novo. We have identified five families with OI type V with variable phenotypes, which mimicked classical collagenous OI types. Identified inter- and intrafamilial variability correlated with type of the collagen defect and affected gene. So that, patients who had qualitative collagen defect had higher phenotype variability compared to those who suffered from quantitative collagen defect.

Results of current thesis broaden understanding of Osteogenesis Imperfecta genetics, etiology, pathogenesis and development of a “brittle bone” phenotype. Current work contributes into OI diagnosis, family planning and further OI research with aim to improve quality of life for OI patients.

Location:

Professor A. Linkbergi auditorium, L. Puusepa 8

URL:

hdl.handle.net/10062/65225

Event category:

Defence

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3 Exhibition: Inna Rebane “Åland Landscapes” Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	4 Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	5 Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	6 Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	7 Full moon exploring session (in case the sky is clear) Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	8 Full moon exploring session (in case the sky is clear) Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	9 Veiko Klemmer Exhibition 14.11.19-19.02.2020 Exhibition dedicated to the Estonian national university “Estonia of Ideals. 100 Years of Quests” Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”
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Lidiia Zhytnik „Inter- and intrafamilial diversity based on genotype and phenotype correlations of Osteogenesis Imperfecta“

February